Effective control of object grasping and manipulation relies on the ability to adjust forces of individual digits to the properties of the object being grasped such as its weight, center of mass or texture. These adjustments rely on (a) detecting object properties through sensory feedback derived primarily from receptors in the fingertips and hand muscles and (b) integrating this feedback with activation of hand muscles appropriate for grasping and manipulation. However, the fine tuning of hand muscle activity to object properties can be disrupted by a number of neurological and musculo-skeletal diseases such as Carpal Tunnel Syndrome (CTS). This compresion neuropathy of the median nerve is one of the most common and debilitating diseases affecting hand function. CTS results in self-reported loss of manual dexterity (e.g., difficulties with fine manipulation, dropping objects, etc.) which is due to somatosensory deficits in the thumb, index, middle and lateral half of the ring finger, and, in severe cases, motor deficits in the thumb. As whole- hand grasping require sensing object properties from all digits to accurately adjust their forces, the study of CTS offers a unique opportunity to improve our understanding the mechanisms underlying sensorimotor integration during whole-hand grasping and manipulation. This primary objective will be pursued by using CTS as a research model to address these important questions of sensorimotor control of grasping. An additional secondary objective is to use the results of the proposed research to improve our understanding of the extent to which increasing impairment in nerve function affects sensorimotor transformations necessary for learning and executing specific aspects of skilled object manipulation. We will pursue two Specific Aims: (1) to quantify the extent to which patients with CTS are able to coordinate all digit forces and contact points when altering object properties (center of mass, weight and texture) and their predictability during five-digit grasping; and (2) to determine the extent to which patients with CTS are able to coordinate digit forces as a function of the number of digits (two, three, four, and five) involved in the grasp. In both Aims, multi-dimensional measures of grasp control from patients with mild and moderately severe CTS will be compared with those obtained from age- and gender-matched healthy controls. PUBLIC HEALTH RELEVANCE. The objectives of the proposed research are relevant to public health as they address a debilitating neuromuscular disease of the hand, Carpal Tunnel Syndrome (CTS), that affects the quality of life in 6 to 14 million adults in the United States. We propose to use CTS as a model to improve our understanding of the mechanisms underlying sensorimotor integration responsible for skilled object manipulation. The knowledge gained through our proposed research will provide significant insight into how electrodiagnostic measures of nerve function relate to specific aspects of grasp control, thus improving the interpretability and applications of these clinical measures. [unreadable] [unreadable]